AMPA receptors are coupled to the nitric oxide/cyclic GMP pathway in cerebellar astroglial cells.
In cultured rat cerebellar astroglia kainate induces cGMP formation with low potency (EC50 310 microM). In the presence of cyclothiazide, a blocker of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor desensitization, the effect of kainate was potentiated and glutamate and AMPA elicited large increases (> 100-fold) in cGMP levels. The response to all three agonists was abolished by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine and required extracellular calcium. Uptake of Co2+ was induced by AMPA in a limited population of astroglial cells and this effect was potentiated by cyclothiazide. These results indicate that calcium-permeable AMPA receptors mediate stimulation of nitric oxide formation in cerebellar astroglia. This effect may be relevant for glutamate-dependent synaptic plasticity processes in the cerebellum.
Baltrons
M A
MA
Instituto de Biología Fundamental V. Villar Palasi and Departamento de Bioquímica y Biología Molecular, Universidad Autónoma de Barcelona, Bellaterra, Spain.
García
A
A
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D003035:Cobalt / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018091:Receptors, AMPA; D009569:Nitric Oxide; D003035:Cobalt; D018698:Glutamic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D006152:Cyclic GMP; D007608:Kainic Acid; D002118:Calcium